The purpose of the proposed research is to study the activity of cytotoxic and inhibitory immunopathologic mechanisms operating in EAS and in patients with Sjorgren's Syndrome. In the first experiments, cell-mediated cytotoxicity (CMC), antibody-mediated cytotoxicity (AbC), and antibody-dependent cell-mediated cytotoxicity (ADCC) activity will be measured in lymphocytes and sera of rats during the course of EAS. Additionally, inhibitory antibody blocking activity and suppressor cell activity will be measured during recovery from EAS. Cytotoxicity will be measured by reacting immune sera or lymphocytes in vitro with Cr-51 labeled submandibular gland target cells and measuring target cell lysis by release of Cr-51 from killed cells. Additional experiments will measure the cytotoxic CMC, AbC, and ADCC activities and antibody blocking and suppressor cell activities in animals protected from development of EAS. Resolution of EAS lesions or protection from lesions may be mediated by activation of inhibitory processes which turn off cytotoxicity. The tissue specificity of the cytotoxicity and inhibitory reactions will be measured during the development of EAS by testing immune lymphocytes and sera with target cells prepared from several organs and rat strains. It is hoped that sufficient definitive information will be gained to provide an increased understanding of the immunopathologic mechanisms operating in EAS.